The long-term objective of this Mentored Patient-Oriented Research Career Development (K23) Award is to develop the candidate's skills in patient-oriented clinical research so that he may become an independent researcher in the field of child mental health. Dr. Chang's specific goal is to gain proficiency in pediatric mood disorders research, specifically in the area of utilizing brain imaging techniques to elucidate neurobiological data correlated to clinical presentations of children and adolescents with bipolar disorder (BD). To accomplish this goal, the candidate will be mentored by experts in the field of neuroimaging, childhood and adult BD, and statistics and research design. The candidate furthermore will participate in educational activities in his department as well as formal coursework in the areas of cognitive neuroscience, brain imaging, and statistics. Finally, the candidate will carry out a research project closely aligned with his research training plan. The goal of the proposed research project is to gather longitudinal phenomenological and brain imaging data on child and adolescent offspring of parents with BD, who are at high risk for developing bipolar disorder. These at-risk children, some already with BD, and healthy controls will be assessed longitudinally over three years by brain functional magnetic resonance imaging (fMRI) and proton magnetic resonance spectroscopy (MRS). fMRI tasks will be related to emotion and attention, and proton MRS will be of bilateral dorsolateral prefrontal cortices (DLPFC), specifically assessing n-acetyl aspartate/creatinine (NAA/Cr) ratios. Phenomenology will be assessed through structured diagnostic interviews, clinician-rated scales, and patient-rated questionnaires. We hypothesize that (1) at-risk offspring already with BD at baseline will have differing areas of activation and deactivation than healthy controls, primarily in DLPFC and anterior cingulate cortex (ACC), (2) at-risk offspring with BD will have lower NAA/Cr ratios in bilateral DLPFC compared to healthy controls, and (3) at-risk offspring who develop BD in the course of this study will demonstrate a greater decrease in DLPFC NAA/Cr from baseline than controls and patterns of brain activation similar to those subjects already with BD, either at baseline or at three-year follow-up. Through conducting this research project and implementation of the research training plan, Dr. Chang plans to become an independent investigator in the field of pediatric BD and thus contributing to the current knowledge of the neurobiology and development of BD.